BACKGROUND AND OBJECTIVES:

The Rotacaps®/Rotahaler® system is a single unit dose inhaler being developed to deliver inhaled salmeterol/fluticasone propionate combination (SFC) as an alternative treatment option to the metered dose inhaler and the multi-dose dry powder inhaler, Diskus®. The aim of this study was to compare the systemic exposure of SFC 50/100 µg following delivery via the Rotacaps®/Rotahaler® and the Diskus®.

 

METHODS:

This was an open-label, randomized, cross-over, repeat-dose (3.5 days of twice-daily dosing) study comparing salmeterol and fluticasone propionate systemic exposure following inhaled SFC 50/100 µg delivered via the Rotacaps®/Rotahaler® and Diskus®, in healthy subjects. Pharmacokinetic sampling was conducted over 12 h post-dose on the last day of each treatment. Pharmacokinetic samples were analysed using solid phase extraction followed by high performance liquid chromatography/tandem mass spectrometry. Co-primary endpoints were fluticasone propionate area under the concentration-time curve over the dosing interval (AUC0-τ ) and salmeterol maximum plasma concentration (C max) on the last day of treatment.

 

RESULTS:

Following SFC 50/100 µg Rotacaps®/Rotahaler®, fluticasone propionate and salmeterol systemic exposures were comparable with Diskus® in terms of both AUC0-τ [geometric mean ratio (GMR) with 90 % confidence interval (CI) of Rotahaler®/Diskus® for fluticasone propionate: 0.98 (0.91, 1.06) and salmeterol: 1.04 (0.99, 1.10)] and C max [GMR (90 % CI) for fluticasone propionate: 1.04 (0.94, 1.15) and salmeterol: 0.97 (0.87, 1.08)], meeting the pre-defined criteria for comparability (upper limit of the 90 % CI for the GMRs (Rotahaler®/Diskus®) ≤1.25]. SFC delivered from both inhalers was well tolerated.

 

CONCLUSIONS:

SFC 50/100 µg Rotacaps®/Rotahaler® showed comparable fluticasone propionate and salmeterol systemic exposure to Diskus® for all pharmacokinetic endpoints with GMR and both upper and lower limits of 90 % CIs within conventional acceptance criteria for bioequivalence (0.8, 1.25), sufficient for considering progression of the Rotacaps®/Rotahaler® product for further clinical development.